The present invention concerns a spinal fluid driven artificial organ device and a method for its use. In particular, this artificial organ, when it contains pancreatic islet cells, can be utilized to treat Type I diabetes mellitus. In addition, the artificial organ can be utilized with other types of cells in order to treat a whole range of diseases requiring endocrine replacement therapy.
Transplantation of islets of langerhans, including intracerebral or intrathecal transplantation, has been proposed to treat diabetes (Jansson, L., and S. Sandler, Transplantation Proceedings (1990), volume 22, pages 775-776; Tze et al, Transplantation (1986), volume 41, pages 531-534). However, the number of islets needed to cure diabetes in rodents is so large that the size of the graft usually exceeds the diffusion distance for oxygen (Jansson, L., and S. Sandler, Transplantation Proceedings (1990), volume 22, pages 775-776), and revascularization can lead to graft rejection (Menger, M. D., S. Jaeger, P. Walter, F. Hammersen, and K. Messmer, Transplantation Proceedings (1990), volume 22, pages 802-803). The diabetic state itself can also adversely affect islet transplantation (Warnock, G. L., N. M. Kneteman, and R. V. Rajotte, Transplantation Proceedings (1990), volume 22, pages 804-805). In addition, there is growing evidence that type I (insulin dependent) diabetes is an autoimmune disease. The immunogenicity of islet cells remains a major obstacle to the use of islet transplantation (Sun, A. M., Methods in Enzymology (1988), volume 137, page 576). Thus, graft rejection and autoimmune destruction of transplanted pancreatic islets are major problems (Fan, M., Z. Lum, X. Fu, L. Levesque, I. Tai and A. Sun, Diabetes (1990), volume 39, page 519).
Current attempts to ameliorate the effects of Parkinsonism by using adrenal cells or fetal substantia nigra cells transplanted directly into the brains of humans have produced transient improvements only. Moreover, the long term effects and possible auto-immune reactions to such direct intracerebral transplants is a continuing cause for concern.
The possibility of utilizing live tissue in an implantable device, comprised of a synthetic membrane, for the purpose of organ replacement was first established in the late 1970s (Galletti, P. M., Colloque Inserm (1989), volume 177, pages 3-12). Such immuno-isolated transplants must have a permeable membrane which allows the transport of nutrients and chemical messengers from the environment to the tissue and which allows the release of effector substances from that tissue into the appropriate body site. Some requirements of the membrane are described in Galletti, P. M., "The Concept of "Bioartificial Endocrine Organs", Colloque Inserm (1989), volume 177, pages 3-12.
In general, two techniques have been utilized: microencapsulation and macroencapsulation. Microencapsulation involves encapsulating a cell or cell cluster with a permeable polymer gel with subsequent injection into the body. Macroencapsulation involves sealing cell suspensions into permeable tubular membranes and subsequently implanting the tubes into the body. Use of immuno-isolated transplants has been proposed to treat type I (insulin dependent) diabetes. Microencapsulation of islet cells has been used to treat diabetes in rats and humans (Fan, M., Z. Lum, X. Fu, L. Levesque, I. Tai and A. Sun, Diabetes (1990), volume 39, page 519; Wu, Z. G., Z. Q. Shi, Z. N. Lu, H. Yang, F. Y. Shi, X. R. Zheng, and A. M. Sun, Trans. Am. Soc. Artif. Intern. Organs (1989), volume 35, pages 736-738). However, disadvantages of microencapsulation and macroencapsulation include (1) biocompatibility of the artificial membrane, (2) fibrosis associated with tubes which inhibit the entrance of nutrients and oxygen and the exit of products, thus compromising in vivo survival of the cells and preventing the device from being operable for a sufficient time, and (3 ) long diffusion distances associated with thick membranes or large tissue chambers.
The present invention lacks the disadvantages and shortcomings of the prior art and provides a spinal fluid driven device and method for treating diseases. One advantage of the present device is that it will successfully isolate cells from the problem of the abnormal microangiopathic environment and it makes it much easier to control the hyperglycemic state because of the lag between the blood sugar level and the spinal fluid level, which tends to be slower to respond to changes in blood sugar level, thus blunting the effects of sudden surges in blood sugar level.